TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20710	62353;62354;62355	chr2:178589597;178589596;178589595	chr2:179454324;179454323;179454322
N2AB	19069	57430;57431;57432	chr2:178589597;178589596;178589595	chr2:179454324;179454323;179454322
N2A	18142	54649;54650;54651	chr2:178589597;178589596;178589595	chr2:179454324;179454323;179454322
N2B	11645	35158;35159;35160	chr2:178589597;178589596;178589595	chr2:179454324;179454323;179454322
Novex-1	11770	35533;35534;35535	chr2:178589597;178589596;178589595	chr2:179454324;179454323;179454322
Novex-2	11837	35734;35735;35736	chr2:178589597;178589596;178589595	chr2:179454324;179454323;179454322
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-38
• Domain position: 43
• Structural Position: 45
• Q(SASA): 0.6259
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/Q	None	None	1.0	N	0.683	0.416	0.309839678437	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.4482	ambiguous	0.5065	ambiguous	-0.218	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
K/C	0.7809	likely_pathogenic	0.8496	pathogenic	-0.387	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
K/D	0.7691	likely_pathogenic	0.817	pathogenic	0.171	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
K/E	0.3462	ambiguous	0.393	ambiguous	0.217	Stabilizing	0.999	D	0.694	prob.neutral	N	0.508648597	None	None	N
K/F	0.8565	likely_pathogenic	0.9117	pathogenic	-0.217	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
K/G	0.6501	likely_pathogenic	0.7395	pathogenic	-0.48	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
K/H	0.4117	ambiguous	0.4769	ambiguous	-0.735	Destabilizing	1.0	D	0.598	neutral	None	None	None	None	N
K/I	0.4456	ambiguous	0.492	ambiguous	0.412	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/L	0.452	ambiguous	0.5412	ambiguous	0.412	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
K/M	0.3765	ambiguous	0.4614	ambiguous	0.154	Stabilizing	1.0	D	0.595	neutral	N	0.488538441	None	None	N
K/N	0.6233	likely_pathogenic	0.6727	pathogenic	-0.011	Destabilizing	1.0	D	0.693	prob.neutral	N	0.477435625	None	None	N
K/P	0.6877	likely_pathogenic	0.7304	pathogenic	0.232	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	N
K/Q	0.2066	likely_benign	0.2411	benign	-0.136	Destabilizing	1.0	D	0.683	prob.neutral	N	0.478877203	None	None	N
K/R	0.09	likely_benign	0.1005	benign	-0.227	Destabilizing	0.999	D	0.612	neutral	N	0.470180697	None	None	N
K/S	0.6086	likely_pathogenic	0.6673	pathogenic	-0.587	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
K/T	0.3681	ambiguous	0.4153	ambiguous	-0.365	Destabilizing	1.0	D	0.668	neutral	N	0.47012779	None	None	N
K/V	0.4281	ambiguous	0.4832	ambiguous	0.232	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/W	0.8458	likely_pathogenic	0.9012	pathogenic	-0.16	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
K/Y	0.749	likely_pathogenic	0.8163	pathogenic	0.159	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.